It is now widely known that certain undesirable physiological conditions such as benign prostatic hyperplasia, male pattern baldness, acne vulgaris, seborrhea, androgenic alopecia, hirsutis and prostate cancer are androgen mediated conditions dependent on dihydrotestosterone (DHT). The enzyme 5.alpha.-reductase mediates the conversion of testosterone to the more potent androgen DHT in various target organs. it has been demonstrated that inhibitors of 5.alpha.-reductase (SAR) should block the formation of DHT and ameliorate the above undesirable physiological conditions. At least one 5AR inhibitor, finasteride, is now in the marketplace and is approved for the treatment of benign prostatic hyperplasia. Mocellini, et al., The Prostate 22, 291-299 (1993).
Recently, it has been found that there are at least two 5AR isozymes in humans, Anderson, et al., Proc. Natl. Acad. Sci. USA 87, 3640-44 (1990); Andersson, et al., Nature 354, 159-61 (1991). The two isozymes exhibit some differences in their biochemical properties, genetics and pharmacology. The two 5AR isozymes (usually called type 1 and type 2) are now the subject of considerable research, which has not yet shown clearly the roles which each isozyme plays in the body.
The present invention provides a series of new compounds which are effective inhibitors of the 5AR isozymes.